Increased type II collagen cleavage by cathepsin K and collagenase activities with aging and osteoarthritis in human articular cartilage
1 Genetics Unit, Shriners Hospitals for Children, 1529 Cedar Avenue, Montreal, QC H3G 1A6, Canada
2 Department of Surgery, McGill University, 1650 Cedar Avenue, Montreal, QC H3G 1A4, Canada
3 Département de sciences cliniques, Faculté de Médecine Vétérinaire, Université de Montréal, CP 5000, St. Hyacinthe, QC J2S 7C6, Canada
4 Lady Davis Institute for Medical Research, SMBD-Jewish General Hospital, 3755 Chemin de la Cote Ste-Catherine, Montreal, QC H3T 1E2, Canada
5 Division of Orthopaedic Surgery, Montreal General Hospital, 1650 Cedar Avenue, Montreal, QC H3G 1A4, Canada
Arthritis Research & Therapy 2012, 14:R113 doi:10.1186/ar3839Published: 14 May 2012
The intra-helical cleavage of type II collagen by proteases, including collagenases and cathepsin K, is increased with aging and osteoarthritis (OA) in cartilage as determined by immunochemical assays. The distinct sites of collagen cleavage generated by collagenases and cathepsin K in healthy and OA human femoral condylar cartilages were identified and compared.
Fixed frozen cartilage sections were examined immunohistochemically, using antibodies that react with the collagenase-generated cleavage neoepitopes, C2C and C1,2C, and the primary cleavage neoepitope (C2K) generated in type II collagen by the action of cathepsin K and possibly by other proteases, but not by any collagenases studied to date.
In most cases, the staining patterns for collagen cleavage were similar for all three epitopes: weak to moderate mainly pericellular staining in non-OA cartilage from younger individuals and stronger, more widespread staining in aging and OA cartilages that often extended from the superficial to the mid/deep zone of the tissue. In very degenerate OA specimens, with significant disruption of the articular surface, staining was distributed throughout most of the cartilage matrix.
Cleavage of collagen by proteases usually arises pericellularly around chondrocytes at and near the articular surface, subsequently becoming more intense and extending progressively deeper into the cartilage with aging and OA. The close correspondence between the distributions of these products suggests that both collagenases and cathepsin K, and other proteases that may generate this distinct cathepsin K cleavage site, are usually active in the same sites in the degradation of type II collagen.